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Evaluation of Lung Cancer Patient Response to First-Line Chemotherapy by Integration of Tumor Core Biopsy Metabolomics with Multiscale Modeling

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Abstract

The standard of care for intermediate (Stage II) and advanced (Stages III and IV) non-small cell lung cancer (NSCLC) involves chemotherapy with taxane/platinum derivatives, with or without radiation. Ideally, patients would be screened a priori to allow non-responders to be initially treated with second-line therapies. This evaluation is non-trivial, however, since tumors behave as complex multiscale systems. To address this need, this study employs a multiscale modeling approach to evaluate first-line chemotherapy response of individual patient tumors based on metabolomic analysis of tumor core biopsies obtained during routine clinical evaluation. Model parameters were calculated for a patient cohort as a function of these metabolomic profiles, previously obtained from high-resolution 2DLC-MS/MS analysis. Evaluation metrics were defined to classify patients as Disease-Control (DC) [encompassing complete-response (CR), partial-response (PR), and stable-disease (SD)] and Progressive-Disease (PD) following first-line chemotherapy. Response was simulated for each patient and compared to actual response. The results show that patient classifications were significantly separated from each other, and also when grouped as DC vs. PD and as CR/PR vs. SD/PD, by fraction of initial tumor radius metric at 6 days post simulated bolus drug injection. This study shows that patient first-line chemotherapy response can in principle be evaluated from multiscale modeling integrated with tumor tissue metabolomic data, offering a first step towards individualized lung cancer treatment prognosis.

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Acknowledgments

DMM, VvB, HBF acknowledge support by National Cancer Institute Grant R15CA203605 (Frieboes).

Conflict of interest

The authors declare no known conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA

    Hunter A. Miller, Donald M. Miller & Hermann B. Frieboes

  2. James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Donald M. Miller, Victor H. van Berkel & Hermann B. Frieboes

  3. Department of Medicine, University of Louisville, Louisville, KY, USA

    Donald M. Miller

  4. Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, KY, USA

    Victor H. van Berkel

  5. Department of Bioengineering, University of Louisville, Lutz Hall 419, Louisville, KY, 40292, USA

    Hermann B. Frieboes

  6. Center for Predictive Medicine, University of Louisville, Louisville, KY, USA

    Hermann B. Frieboes

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  1. Hunter A. Miller
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Correspondence to Hermann B. Frieboes.

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Miller, H.A., Miller, D.M., van Berkel, V.H. et al. Evaluation of Lung Cancer Patient Response to First-Line Chemotherapy by Integration of Tumor Core Biopsy Metabolomics with Multiscale Modeling. Ann Biomed Eng 51, 820–832 (2023). https://doi.org/10.1007/s10439-022-03096-8

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